Dr. Phil KarpowiczBiological Sciences, University of Windsor
The timing of cancer
Co-Investigators and Collaborators:
- Dr. John Hogenesch, Perinatal Institute, Cincinnati Children’s Hospital
EVIDENCE OF PROGRESS
Our body can tell time of day: light, which is detected by our eyes, sends a signal to our brain and then throughout our body. This system of body timing by light is called the circadian clock, and it controls our sleep and wake cycles, and the 24 hour activity of many organs and tissues. Circadian clocks exist in all cells in our body, but the consequences of changing our waking versus sleeping cycles are only starting to be appreciated.
Our research team, at the University of Windsor, specializes in the study of stem cells and regeneration. Supported by the Seeds4Hope program, we have recently completed a study that shows the risks of changing our sleep/wake cycle. Using mice, we found that intestinal healing occurs in circadian rhythms. When these rhythms are lost, the intestine cannot regenerate effectively from injuries caused by radiation damage. The radiation damage that we studied in mice is very significant to cancer treatment because it is very similar to Gastrointestinal Mucositis, an illness in patients that emerges as a side effect of radiation therapy. In our work, we found that cells in the intestine divide at specific times of day. When circadian clocks were dysfunctional in these cells, they did not time their division with other daily processes that happen in the intestine. Instead, these cells started to divide prematurely and did not respond to inflammation that is needed for successful healing. Importantly, the genes involved in this process in mice are known to drive cancer in humans. This means we can build on this research to find clinically-relevant information. Colorectal cancer is an illness that starts with uncontrolled cell division, and our research will find out whether a daily timing is lost in cancer cells. We will also find out all the genes involved using intestinal stem cell cultures. We have started this work using mice, and have assembled a team of two graduate students, one medical student, and two undergraduates to complete this work soon.
Colorectal cancer is the third most common cancer in Canada, and has a higher incidence in the Windsor-Essex region than the Ontario average. The Windsor-Essex region has a history of industry which involves shift-work. Shift-workers, whose waking/sleeping cycles are artificially changed, are prone to many gastrointestinal diseases, including colorectal cancer. Translating this research in the future may be as simple as avoiding frequent sleep interruptions, for people who are susceptible to colorectal cancer. This makes our proposal particularly relevant for cancer prevention, and for the Seeds4Hope program.
MEASURES OF PROGRESS
A) Manuscripts and Publications: One manuscript was submitted in September, 2016
B) Conference Presentations: One abstract was published at the 3rd Biennial International Cancer Research Conference in Windsor, Canada
C) Grants Received/Applied For: Two grants submitted: CIHR Project Scheme grant and Ontario Institute of Regenerative Medicine
D) Training of Highly Qualified Personnel:
Graduate Students: Kyle Stokes (Ph.D., 2016); Malika Nunes (M.Sc., 2015)
Senior Undergraduate Students: Anna Mierzwa, Abrial Cooke, and Celina DeBiasio